Terminal deoxynucleotidyl transferase, an unusual DNA polymerase which does not accept template instruction, is normally found only in thymus and bone marrow cells. This enzyme activity is highly elevated in bone marrow and peripheral blood of patients with certain types of human leukemia as well as in some human lymphoblastoid cell lines. The long range objective of this research program is to (1) identify the marrow cells which contain terminal transferase (2) define the cellular role of terminal transferase (3) investigate its possible role in the immune system and (4) study the fate of terminal transferase containing cells as they differentiate. We have developed techniques to enrich the marrow by 60 fold in terminal transferase containing cells so that we can identify the cell and study its differentiation in tissue culture. Affinity chromatography purification techniques we have developed will allow us to characterize this enzyme from a number of mammalian sources. One metabolic consequence of severe immune dysfunction which we have recently reported is a gross perturbation of the normal deoxynucleotide pool in cells. This may represent a model for malfunctioning of terminal transferase in the immune system.